A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Chinese Subjects With Post-stroke Upper Limb Spasticity

NCT01153815 | Completed Phase 3 Results

• 1 other identifier: 112958
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 13

Brief Summary

This trial is a multicenter, double-blind, randomized, placebo-controlled study to compare GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox") with placebo on the efficacy and safety of treatment in poststroke subjects with focal wrist, finger and in some cases, thumb spasticity. Approximately 168 subjects will be enrolled. Subjects will receive a single treatment session of intramuscular GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox") '200U or 240U (if thumb spasticity is present)' or placebo in a randomization ratio of 1:1. The subjects will be observed until 12 weeks post injection. Outcome measures include changes from baseline at every post injection visit as measured on the Modified Ashworth Scale (MAS), Disability Assessment Scale (DAS) and Global Assessment Scale. The primary efficacy endpoint is the change from baseline at week 6 for wrist flexor muscle tone as measured on the Modified Ashworth Scale. Safety parameters will also be measured including adverse events, vital signs (pulse and blood pressure) and clinical laboratory tests (haematology, serum chemistry and urinanalysis).

Conditions

Cerebrovascular Accident

Keywords

efficacy; Spasticity, Post-Stroke; safety; Botulinum toxin type A; placebo; spasticity

Outcome Measures

Primary Outcomes (1)

• Change From Baseline at Week 6 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS)

  The investigator, physiotherapist, or occupational therapist extended the participant's wrist as quickly as possible to grade flexor muscle tone. The MAS wrist score was calculated by using the 6-point MAS (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension). Change from Baseline at Week 6 was calculated as the value at Week 6 minus the value at Baseline.

  Baseline (Day 0) and Week 6

Secondary Outcomes (8)

• Area Under the Curve (AUC) for the Change From Baseline at Weeks 6 and 12 for MAS Wrist Score

  Baseline (Day 0), Week 6, and Week 12

• Change From Baseline at Weeks 1, 4, 8, and 12 for Wrist Flexor Muscle Tone as Measured on the MAS

  Baseline (Day 0) and Weeks 1, 4, 8, and 12

• Number of Participants Classified as Wrist Treatment Responders at All Post-injection Visits

  Weeks 1, 4, 6, 8, and 12

• Change From Baseline at Weeks 1, 4, 6, 8, and 12 for Finger Flexor Muscle Tone as Measured on the MAS

  Baseline (Day 0) and Weeks 1, 4, 6, 8, and 12

• Change From Baseline at Weeks 1, 4, 6, 8 and 12 for Thumb Flexor Muscle Tone as Measured on the MAS

  Baseline (Day 0) and Weeks 1, 4, 6, 8, and 12

Study Arms (2)

placebo

PLACEBO COMPARATOR

Sodium chloride

Drug: placebo

GSK1358820(Botulinum Toxin Type A)

EXPERIMENTAL

GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox")

Drug: GSK1358820(Botulinum toxin type A)

Interventions

GSK1358820(Botulinum toxin type A) DRUG

GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox")

Also known as: OnabotulinumtoxinA, Botox

GSK1358820(Botulinum Toxin Type A)

placebo DRUG

placebo

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria:
• Subjects with upper limb spasticity who are at least 6 months post stroke and present with spasticity of both the wrist and fingers in the study limb.
• Wrist flexor muscle tone of 3 or greater and finger flexor muscle tone of 2 or greater as measured on MAS (0 to 4).
• At least one functional disability item (i.e., hygiene, dressing, pain, or cosmesis) with a rating of 2 or greater on DAS (0 to 3).
• If using oral anti-spasticity medications, must be stable for at least 1 month prior to study enrolment
• If using physical therapy, must be stable for at least 1 month prior to study enrolment.
• Male or female 18 to 75 years old at the time of informed consent.
• \>=40kg in weight.
• QTc criteria: (either QTcb or QTcf, machine or manual overread, males or females); include the following details as appropriate: QTc\<450 millisecond (msec) or \<480msec for subjects with Bundle Branch Block-values based on either single electrocardiogram (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording period.
• Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2xULN; alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin \>1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• In the opinion of the investigator, subject must clearly understand the intent of the study and be willing and able to comply with study instructions and complete the entire study.
• Informed consent has been obtained.

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Presence of fixed contracture of the study limb (absence of passive range of motion).
• Profound atrophy of muscles to be injected (in the investigators opinion).
• Infection or dermatological condition at the injection sites.
• Significant inflammation in the study limb limiting joint movement.
• History of or planned treatment for spasticity with phenol or alcohol block in the study limb.
• History of or planned surgical intervention for spasticity of the study limb.
• History (within 3 months of qualification) of or planned (during study period) casting of the study limb.
• Participation in another clinical study currently, or within the 30 days immediately prior to enrolment.
• Previous or current botulinum toxin therapy of any serotype.
• Planned or anticipated initiation of new antispasticity medications during the clinical study.
• Any medical condition that may put the subject at increased risk with exposure to GSK1358820, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might have interfered with neuromuscular function.
• Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function. A full list of prohibited medications that interfere with neuromuscular transmission is provided as Appendix 1.
• Current treatment for spasticity with an intrathecal baclofen.
• Females who are pregnant, nursing, or planning a pregnancy during the study period, or females of childbearing potential, not using a reliable means of contraception.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Guangzhou, Guangdong, China

Location

GSK Investigational Site

Haerbin, Heilongjiang, 150001, China

Location

GSK Investigational Site

Wuhan, Hubei, 430060, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Suzhou, Jiangsu, 215004, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110001, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Beijing, 100050, China

Location

GSK Investigational Site

Beijing, 100068, China

Location

GSK Investigational Site

Beijing, 100730, China

Location

GSK Investigational Site

Hangzhou, 310016, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

MeSH Terms

Conditions

Stroke; Muscle Spasticity

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 30, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: June 28, 2017
• Results First Posted: May 17, 2012

Record last verified: 2017-01

Locations

CN (13)